Is CD300C p.Ser40Gly (c.118A>G) pathogenic?

CD300C p.Ser40Gly (c.118A>G) is classified Uncertain significance in CD300C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: likely benign (0.1818); Ultra-rare (popmax 0.0165%, mid).

How common is CD300C p.Ser40Gly (c.118A>G) in the general population?

CD300C p.Ser40Gly (c.118A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD300C p.Ser40Gly (c.118A>G)?

AlphaMissense predicts likely benign (score 0.1818) — an in-silico prediction, not a clinical call.

CD300C p.Ser40Gly

c.118A>G · rs369638601 · VCV2324098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1818	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -11.50	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -0.26, phastCons 0.023
Regional constraint	o/e 0.96	unconstrained · MANE · 4,190 bp · p 0.54 · regional, not allelic
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00297% 48/1,613,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0039%	25,645
African / African-American	0.00133%	75,046

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD300C
Protein: p.Ser40Gly
Coding: c.118A>G
MANE Select: NM_006678
dbSNP: rs369638601
Type: single nucleotide variant
Location: chr17:74544891 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06 · 1 PDB
Residue 40: the ig-like v-type domain

Full CD300C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300C p.Ala13Gly Uncertain significance ★ ⚠ same type
CD300C p.Ala89Thr Uncertain significance ★ ⚠ same type
CD300C p.Ala89Val Uncertain significance ★ ⚠ same type
CD300C p.Arg210Ser Uncertain significance ★ ⚠ same type
CD300C p.Arg44His Uncertain significance ★ ⚠ same type
CD300C p.Arg44Pro Uncertain significance ★ ⚠ same type
CD300C p.Glu126Lys Uncertain significance ★ ⚠ same type
CD300C p.Glu170Lys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd300c-p-ser40gly (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown